Recent experimental studies support the concept of a dynamic interaction between the immune system and the central nervous system. Furthermore, psychologic stress has been shown to adversely affect the mammalian host's immune response. This study is designed to examine the mechanisms of stress-induced immunosuppression. Specifically, the aims of this project are to examine the mechanisms by which restraint-stress alters the host's immune response to herpes simplex type 1 - induced encephalitis in the mouse model. In addition, concurrent alterations in the viral pathogenesis of the disease will be evaluated. During the course of a herpes simplex-induced encephalitis in the mouse, significant destruction of the central nervous system occurs. In response to the infection, inflammatory infiltrates, consisting of T lymphocytes, B lymphocytes, natural killer cells, macrophages and granulocytes localize to the area of viral replication. However, it has been strongly suggested that the both lymphokine-secreting and cytolytic T cells are critical for an effective host response. Therefore, the effects of stress on T cell activation (cytokine gene expression) and lymphocyte trafficking to sites of infection will be important parameters to evaluate in this study. While some investigators have demonstrated significant pathosis results from antiviral T cell responses, we hypothesize that stress-induced immunosuppression will be detrimental to the host as unimpeded viral replication will occur in the CNS. This experimental model will allow direct comparisons between stressed and non-stressed animals with respect to viral pathogenesis and immune responses.